The purpose of this program project is to develop and characterize polymorphisms that will be informative for studies of human genome diversity and to develop mathematical methods for evaluating population variation and evolution based on these polymorphisms. In my subproject we hope to contribute polymorphisms and data reflecting maternal inheritance, paternal inheritance, and Mendelian inheritance. Our specific goals are the following: 1. Maternal inheritance: mtDNA. Sequence variable regions of mtDNA of individuals from human populations sampled for the HGDP. In collaboration with Dr. Slatkin's group analyze mtDNA sequence diversity so as to evaluate past evolutionary events such as divergence times, population growth, migration, and subsequent secondary population contact. 2. Paternal inheritance: Y-chromosome. Working with a small sample of individuals from all parts of the world (i.e., not specifically Europeans), identify PCR-based short-sequence-repeat polymorphisms specific to nonrepetitive portions of the Y chromosome. Construct Y chromosome haplotypes for males from selected populations to determine the level of variability at each locus and variability in linkage disequilibrium among loci. 3. Mendelian inheritance: T cell receptor sequences. Genotype individuals from selected populations worldwide for known single nucleotide polymorphisms in T cell receptor alpha and beta chain sequences. Determine variability at each polymorphic site and for each region. Evaluate differences in disequilibrium of the same region among populations.